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Titolo:
FUNCTIONAL COUPLING OF HUMAN METABOTROPIC GLUTAMATE-RECEPTOR HMGLU(1D) - COMPARISON TO SPLICE VARIANTS HMGLU(1A) AND HMGLU(1B)
Autore:
HILTSCHER R; SEUWEN K; BODDEKE HWGM; SOMMER B; LAURIE DJ;
Indirizzi:
NOVARTIS PHARMA AG,ROOM 809,BLDG 386 CH-4002 BASEL SWITZERLAND NOVARTIS PHARMA AG CH-4002 BASEL SWITZERLAND
Titolo Testata:
Neuropharmacology
fascicolo: 7, volume: 37, anno: 1998,
pagine: 827 - 837
SICI:
0028-3908(1998)37:7<827:FCOHMG>2.0.ZU;2-8
Fonte:
ISI
Lingua:
ENG
Soggetto:
LONG-TERM POTENTIATION; G-PROTEIN ACTIVATION; MGLUR1 MUTANT MICE; KIDNEY-CELL-LINE; RAT-BRAIN; SIGNAL TRANSDUCTION; MGLU(1) RECEPTOR; PHOSPHOLIPASE-C; EXPRESSION; DOMAIN;
Keywords:
HUMAN METABOTROPIC RECEPTOR; MGLU(1D); AEQUORIN LUMINESCENCE; INOSITOL MONOPHOSPHATE; CALCIUM FLUORESCENCE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
54
Recensione:
Indirizzi per estratti:
Citazione:
R. Hiltscher et al., "FUNCTIONAL COUPLING OF HUMAN METABOTROPIC GLUTAMATE-RECEPTOR HMGLU(1D) - COMPARISON TO SPLICE VARIANTS HMGLU(1A) AND HMGLU(1B)", Neuropharmacology, 37(7), 1998, pp. 827-837

Abstract

Functional coupling of the human mGlu(1) splice variants was examinedby heterologous expression. In cells stably (CHO) or transiently (A9)expressing the hmGlu(1d) receptor, agonists elevated intracellular calcium with a rank order of potency typical of a group I mGlu receptor (quisqualate > L-glutamate > (S)-dihydroxyphenylglycine > (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R -ACPD)). These responses were reduced by the antagonist(+)-alpha-methyl-4-carboxyphenylglycine (MCPG), by pretreatment with pertussis toxin and phorbol eater, and byremoval of extracellular calcium. In transiently transfected HEK293 cells, the hmGlu(1b) and -(1d) receptors increased inositol monophosphate (IP) production only in the presence of glutamate, whereas hmGlu(1a) coupled even in the absence of agonist. This was not due to differences in receptor expression levels as assessed by immunoblotting. Adenylate cyclase activity in HEK293 cells expressing the hmGlu(1) variantswas neither stimulated nor inhibited by glutamate. In A9 cells hmGlu(1a)-mediated calcium/fluo-3 fluorescence was sensitive to depletion ofintracellular calcium stores by thapsigargin, but the hmGlu(1d) response was resistant. Thus, hmGlu(1d) receptors can be distinguished fromhmGlu(1a) by their lack of agonist-independent coupling and their dependence on extracellular calcium. (C) 1998 Elsevier Science Ltd. All rights reserved.

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Documento generato il 02/12/20 alle ore 13:47:49